KR100697093B1 - Double-Cell Formulations Containing Vitamin C and Cold Remedy and Methods for Making the Same - Google Patents

Abstract

The present invention relates to a double tablet consisting of a first layer containing a vitamin granule mixture and a second layer containing a cold therapeutic granule mixture. The present invention also comprises the steps of pulverizing the cold therapeutic active ingredient mixture to adsorb to the inorganic carrier; Tableting into a double tablet consisting of a first layer containing a vitamin granule mixture and a second layer containing a cold therapeutic granule mixture; Coating the double tablet with a first transparent coating substrate; The present invention relates to a method for preparing a double tablet containing a vitamin C and a cold therapeutic agent comprising the step of double coating a second transparent coating base containing a sweetening agent and a flavoring agent on the transparent coating.

Vitamin C, Cold Remedy, Double Tablet

Description

A double-layer dosage form containing vitamin C and common cold therapeutic agent and a method of preparing the dosage form

The present invention relates to a double tablet composition of a cold treatment agent stable during the shelf life and a method for preparing the same. More specifically, after preparing the first-layer granules containing vitamins and the second-layer granules containing the main ingredients of the cold treatment agent, uncoated tablets are prepared using a double tableting tablet machine, which has a refreshing taste and aroma of vitamins, and is moisture-proof. The present invention relates to a double tablet containing a vitamin and a cold treatment agent prepared by coating with a strong transparent film coating, and a method of manufacturing the same.

Cold medicines have been developed by mixing and formulating one or more active ingredients with the aim of alleviating the symptoms of various colds. Cold medicines used in this way include ingredients for antipyretic, analgesic, antitussive, expectorant, antihistamine, bronchial expansion, nasal congestion. Acetaminophen is mentioned as an example of the component used widely for antipyretic and analgesic purposes. Acetaminophen is widely used for the reduction of fever, toothache, neuralgia, muscle pain, and rheumatic pain caused by colds and is marketed as a tablet, hard capsule, liquid, syrup and the like. Ibuprofen or dexbutrofen are used for the same purpose, and they are also widely known to have analgesic, anti-inflammatory and antipyretic effects. Therefore, these drugs are commonly used for fever and pandemic symptoms including colds. In addition, ethenamide, phenacetin, etc. are also used for antipyretic and analgesic purposes. Further, for the purpose of antitussive purposes, dextromethorphan hydrobromide, noscapine hydrochloride, trimethoquinol hydrochloride, chlorophenylamine d-maleic acid, carbetapentane citrate, tifepidine citrate, cloperastine hydrochloride, pendizocloferastine hydrochloride , Thievepidine hydrochloride, ephedrine hydrochloride, phenylephrine hydrochloride, and the like, for example, guifenesin, potassium guayacolsulfonic acid potassium, d-maleic chlorophenylamine, etc. for antihistamine purposes Dl-methyl-ephedrine hydrochloride, lysozyme chloride, ceratiopeptidase, etc., for anti-inflammatory purposes; pseudoephedrine hydrochloride, phenylpropanolamine, dipexamide, phenylaminopropanol hydrochloride , Oxymethazolin, xylmethazoline, etc. are used.

In general, vitamin C is recommended along with cold medicine at the pharmacist's recommendation, and commercially available cold medicine products contain a small amount of vitamin C. The effects of vitamin C on colds have not been shown to be negligible or proven alone, but recently several papers have shown excellent cold suppression and prevention effects when combined with cold medicines. In particular, the papers described in the International Journal of Clinical Pharmacology and Therapeutics, 41 (3), 114-125 (2003) are statistically significant when vitamin C is included in the general cold medicine, especially when acetaminophen is taken with vitamin C. As a result, it has been reported to have a very good effect on the common cold. Similarly, in the papers described in Military Medicine, 169 (11), 920-925 (2004), vitamin C also plays a very large role in respiratory infections, reducing the progression of common cold in 45-91% of people taking vitamin C. It is reported that the incidence of pneumonia is very high, ranging from 80 to 100%.

As the efficacy of the vitamin C as described above, the current cold treatment drugs are mixed, manufactured and sold cold medicine ingredients and vitamins. However, taking into account the fact that the use of a number of the main ingredients in the common cold medicine causes color discoloration and deterioration of the stability of the vitamin C and the physical properties of the main ingredients change or worsen over time, most cold medicines are filled in capsules. Unlike tablets undergoing compression molding, these capsule formulations are filled with empty capsules by filling only two capsules, so they can be divided into two, but if swallowed by taking water, they do not stick to the esophagus. There is this.

Vitamin C, which is used as an antioxidant, is highly reactive, so when it is simply mixed and compressed into tablets, the color changes over time, and the content decreases. In order to shield it, it is sometimes coated with an opaque film with color or mixed with herbal ingredients to make it impossible to see the change of color with the naked eye.Therefore, consumers take cold medicines containing less active ingredients. have. Therefore, in the case of tableting tablets, in consideration of stability, vitamin C is preferably compressed separately from other cold medicine main ingredients.

Single tablets have the advantage of being smaller in size and easier to take than capsules, but are difficult to formulate compared to capsules due to the large amount of excipients required for tableting. In addition, the double tablets are divided into two layers, and the mixing ratio of the excipients that can be used in the case of a synthetic cold medicine having a very high content ratio of the main components constituting the tablet is difficult to prepare a double tablet. Therefore, formulating a cold medicine layer having a high content of the main ingredient together with a layer containing vitamin C so as to be well tableted using a small amount of excipients requires a lot of preparation techniques and controls to prevent the separation of the double tablets between layers.

In particular, simple mixing of acetaminophen and other cold medicine main ingredients among the main ingredients of the general cold medicine is a tableting tablet, which causes a problem of long-term storage. In the present invention, it was possible to improve the defects due to the mixing of the main components through inclusion with a specific inorganic carrier.

Colds are especially easily affected by children and women with weak immunity, so many children and women patients buy cold medicine. Cold medicine is treated by symptomatic therapy, and most of the medicines used are odors and smells, and even when coated or filled with capsules, the taste and smell are reversed, especially when taken by children or women who do not like to take medicine. It is true that even a short time gives a sense of rejection. US 5098715 discloses a film coating using a sweetener and a volatile flavoring agent together with a pigment such as titanium oxide to taste and smell as a tablet coating to mask unpleasant taste. However, not only can not be divided into two parts to treat the pigment, there is a problem that the coating composition is shielded the visual effect of the double tablet with the upper and lower layers separated. In addition, the use of sucrose or powdered sugar with high absorption as a sweetening agent may not show the moisture resistance, which is the main target of the coating, and thus, the stability may be reduced.

The present inventors conducted various studies to increase the stability of the vitamin C and cold therapeutic ingredients, to feel the fresh taste and aroma of vitamin C, and to increase the compliance of patients, especially children and women. As a result, the vitamin C and cold therapy components were separated into a first layer and a second layer, respectively, and then compressed into double tablets having increased stability, and then coated with a film coating material to increase the stability. A very small amount of sweetener and flavoring agent were mixed with a transparent film coating base so as to feel fresh taste and aroma, and sprayed again on a transparent coated double tablet. Thus, the present inventors have completed the present invention by developing a double tablet containing vitamin C and a cold treatment agent that not only increases the stability of the main components and vitamin C, but also satisfies vision, taste, and smell.

Accordingly, it is an object of the present invention to provide a double tablet that increases the stability of the cold therapeutic active ingredient and vitamin C.

In addition, an object of the present invention is to provide a double tablet coated with the double tablet with a moisture-proof film coating for the stability of the active ingredient and vitamin C cold treatment.

In addition, the present invention provides a double-coated double tablet coated with an additional film coating containing a sweetener and a flavoring agent to mask the bitter taste of the cold medicine active ingredient and to mask the very sour and bitter taste of the vitamin C raw material itself. For the purpose of

In addition, an object of the present invention is to add a different pigment to each of the double layer, so that the visual effect of the double tablet with the naked eye, and to provide a double tablet coated with a transparent coating on such a double layer.

The present invention relates to a double tablet consisting of a first layer containing a vitamin granule mixture and a second layer containing a cold therapeutic granule mixture. More particularly, the present invention relates to a double tablet further comprising a first transparent coating layer coated on the double tablet and a second transparent coating layer containing a sweetener and a flavoring agent.

The invention also

1) a step of pulverizing a cold therapeutic active ingredient mixture and adsorbing the inorganic carrier;

2) tableting into a double tablet consisting of a first layer containing a vitamin granule mixture and a second layer containing a cold therapeutic granule mixture;

3) coating the double tablet with a first transparent coating substrate;

4) comprising double coating on the transparent coating with a second transparent coating base containing a sweetener and a flavoring agent,

A method for producing a double tablet containing vitamin C and a cold cure.

Hereinafter, the present invention will be described in detail.

In the present invention, in order to provide stability to a formulation containing vitamin C and a cold treatment agent, a naked tablet is prepared by separating the first layer containing vitamin C and the second layer containing a cold treatment agent. The uncoated tablet thus prepared is coated with a first coating base for moisture proofing, and then coated with a second transparent coating base containing a sweetening agent and a flavoring agent to make the lemon taste and aroma again. Here, the first coating base and the second coating base is transparently coated so that the uncoated tablet form can be seen as a double coating as a transparent coating base.

In addition, the present invention

1) a step of pulverizing a cold therapeutic active ingredient mixture and adsorbing the inorganic carrier;

2) tableting into a double tablet consisting of a first layer containing a vitamin granule mixture and a second layer containing a cold therapeutic granule mixture;

3) coating the double tablet with a first transparent coating substrate;

4) comprising double coating on the transparent coating with a second transparent coating base containing a sweetener and a flavoring agent,

Provided is a method for preparing a double tablet containing vitamin C and a cold cure. Here, the cold therapeutic granule mixture may be prepared by using a fluidized bed granulator by pulverizing the main therapeutic mixture of the cold therapeutic agent using a grinding mixer such as Fit's mill and adsorbing the inorganic carrier, and then spraying the binding liquid. The other granules may be mixed with direct-type excipients to produce granules. The inorganic carrier used herein is a porous material, and in order to adsorb the main ingredient particles to the porous part, the process of pulverizing the main ingredient mixture for cold treatment is essential. The smaller the particle size by grinding the main ingredient mixture for cold treatment, the stronger the adhesion to the inorganic carrier. The inorganic carrier is hydrophilic, which facilitates the release of the main constituents in water, thereby improving the physical properties of the formulation without causing problems of elution, and the ability to support the structure under pressure when adsorbed with the main constituents due to its strong binding and bearing capacity. This is strong.

The vitamin granule mixtures and cold therapeutic agent granule mixtures may be prepared according to conventional methods, and these granular mixtures may be used as vitamin and cold therapeutic active ingredients, as well as pharmaceutically acceptable excipients, disintegrants, binders, glidants, sweeteners, complexes. Fragrances and the like.

As the active ingredient for the treatment of colds in the double tablet of the present invention, all the ingredients generally used in the general cold medicine can be used. For example, acetaminophen, ibuprofen, dexibuprofen, ethenamide, phenacetin and the like can be used for the purpose of antipyretic analgesic, dextromethorphan hydrobromide, noscarpine hydrochloride, trimethinquinol hydrochloride , chlorophenylamine, d-maleic acid, carbetapentane citrate, tifepidine citrate, chloroperastine hydrochloride, pendizocloperastine hydrochloride, tifepidine hydrochloride, ephedrine hydrochloride, phenylephedrine hydrochloride, and the like. Guapenesine, guayacolsulfonic acid potassium, d-maleic acid chlorophenylamine for antihistamine use, dl-methylethylphedrine hydrochloride for bronchial expansion, lysozyme chloride, ceratiope As a decongestant, pseudoephedrine, phenylpropanolamine, dipexamide, phenylaminopropanol hydrochloride, oxymethazolin, xylmethazolin, etc. have.

The main components of the vitamin granule mixture are vitamin C, vitamin A, vitamin B1 (chiamine), vitamin B2 (riboflavin), vitamin B3 (niacin, niacinamide, nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine), vitamin B9 Also includes (folic acid), vitamin B12 (cyanocobalamin), vitamin D (calciferol), vitamin E (tocopherol), vitamin H (biotin) or vitamin K (phylloquinone, menaquinone, menadione) and mixtures thereof can do.

The inorganic carrier used in the present invention is used to increase the homogeneity and physical stability of the main components by adsorbing the main components, preferably microcrystalline cellulose, hard silicic anhydride, bentonite, titanium oxide, talc and the like. In particular, hard silicic anhydride and microcrystalline cellulose are most preferred.

Disintegrants used in the present invention generally use disintegrants such as carboxymethyl cellulose sodium, sodium starch glyconate, hydroxypropyl cellulose, carboxymethyl cellulose calcium which can be orally administered, and carboxymethyl cellulose sodium is most preferred. .

The binders used in the present invention are generally orally administrable polyvinylpyrrolidone or derivatives thereof (PVP K30, BASF), vinyl pyrrolidone / vinyl acetate copolymers (Plasdone S-630, BASF), hydroxypropylmethylcel Loose (HPMC, ShinEtsu), hydroxypropyl cellulose (HPC-L, Nisso) and the like can be used, with Plasdone S-630 and HPC-L being most preferred.

The glidants used in the present invention may generally use oral administration of magnesium stearate, stearic acid, calcium stearate, sucrose fatty acid and the like, and magnesium stearate is most preferred.

The transparent film coating substrate used in the present invention is polyvinyl alcohol (PVA; ABA ^TM ), hydroxypropyl methyl cellulose (HPMC), phthalic acid hydroxypropyl methyl cellulose (HPMCP) and methacrylate dimethylaminoethyl At least one selected from the group consisting of methyl methacrylate copolymer (Eudragit E), and preferably PVA.

The sweeteners used in the present invention are most preferably acesulfame potassium using acesulfame potassium, sucralose, aspartame, stevioside, saccharin and the like which make the sweetness taste in a very small amount.

The flavoring agent used in the present invention is mixed with a volatile aromatic oil in alcohol and used. Volatile aromatic oils are commonly known as essential oils such as menthol, lavender, rosemary, sage, thyme, and peppermint. In addition, it refers to a volatile substance of an oil component that emits various flavors such as fruit flavors such as orange flavor, strawberry flavor, lemon flavor, and apple flavor. Among these various fragrances, lemon flavors and orange flavors are used to flavor the vitamin C. The most preferred flavor is lemon flavor oil.

In the present invention, the vitamin granules and the general cold medicine main ingredient granules are divided into two tablets, and for the visual effect, the vitamin granules and the general cold medicine main ingredient granules are prepared by adding different pigments to have different colors. For example, the vitamin part is yellow and the cold medicine main ingredient part uses a color other than yellow to produce a double tablet with the naked eye. Therefore, the double tablets prepared according to the method of the present invention are divided into vitamin granules and the main ingredient granules of the cold treatment agent, so that they are not only physicochemically stable but also have a visual effect.

In the present invention, the moisture-proof film coating is also performed to enhance physicochemical stability, and the film coating uses a transparent coating substrate (first transparent coating substrate) to maximize the visual effect of the double tablet.

The present invention is also further coated with a coating base containing a sweetener and a flavoring agent to add the effect of taste and smell to the coated double tablet. As described above, for the visual effect of duality, the additional coating substrate also uses a transparent coating substrate (second transparent coating substrate).

In the present invention, the weight ratio of the uncoated tablet to the coating substrate may be used as 1: 0.01 to 0.1.

The sweetener may be used in a ratio of 0.001 to 0.025 relative to the weight of the film coating base material, and preferably in a ratio of 0.002 to 0.020.

The flavoring agent may be used in a ratio of 0.02 to 0.8 with respect to the weight of the film coating base material, and preferably in a ratio of 0.1 to 0.4.

In addition, in the double tablets prepared according to the method of the present invention, the cold therapeutic formulation is not fixed, and one or more of the active ingredients may be omitted or added to the basic formulation, and the formulation may be sterilized and / or preservatives, stabilizers and buffers. Supplements and other therapeutically valuable substances or substances that may be helpful for treatment. The effective cold medicine component may be administered once or in divided doses in conventional dosages.

Hereinafter, the present invention will be described in more detail with reference to the following examples, which are intended to illustrate the present invention but are not intended to limit the scope of the present invention.

Example 1 Preparation of a Double-Formulation Cold Therapeutic Granule Mixture

     Component Content (g / 1,000T)

     Acetaminophen 200

     dl-maleic chlorpheniramine 1.25

     Hydrochloric acid hydrochloride 8

     DL-Methylephedrine Hydrochloride 10

     Pseudohydrophedrine Hydrochloride 15

     Caffeine anhydrous 8.33

     Light anhydrous silicic acid 10

     Microcrystalline Cellulose 25

     Vinyl Pyrrolidone / Vinyl Acetate Copolymer (Plasdone S-630) 8

     Hydroxypropyl Cellulose (HPC-L) 7

     Pigment 0.02

     Titanium Oxide 0.3

     Crosscarboxymethylcellulose Sodium 3

     Magnesium Stearate 5

Acetaminophen, dl-maleic acid chlorpheniramine hydrochloride, cloperate hydrochloride, dl-methylepedrine hydrochloride, pseudoephedrine hydrochloride, and anhydrous caffeine are homogeneously crushed together with inorganic carriers such as hard silicic anhydride and microcrystalline cellulose. And adsorbed, mixed in a fixed vessel, and then completely dissolved with vinyl pyrrolidone / vinyl acetate copolymer (Plasdone S-630), hydroxypropyl cellulose (HPC-L), and pigment in 200 g of water in a fluidized bed granulator. The granules were prepared by spraying a homogeneously suspended binder solution. At this time, the inlet temperature of the fluidized bed granulator was 60 ° C, the outlet temperature was 27 ° C, and the product temperature was 31 ° C. And the spray rate of the bonding liquid was 12rpm, air pressure was 30psi. After dissolving the cross-carboxymethyl cellulose sodium as a disintegrating agent in the prepared granules, and homogeneously mixed, and added magnesium stearate as a lubricant, and homogeneously mixed for 5 minutes, the granule mixture of 300.9g of the total cold medicine part was completed.

Example 1-1 Preparation of Granule Mixture of Double-Defined Cold Therapeutics

     Component Content (g / 1,000T)

     Acetaminophen 200

     dl-maleic chlorpheniramine 1.25

     Hydrochloric acid hydrochloride 8

     DL-Methylephedrine Hydrochloride 10

     Pseudohydrophedrine Hydrochloride 15

     Caffeine anhydrous 8.33

     Light anhydrous silicic acid 10

     Microcrystalline Cellulose 25

     Vinyl Pyrrolidone / Vinyl Acetate Copolymer (Plasdone S-630) 8

     Hydroxypropyl Cellulose (HPC-L) 7

     Pigment 0.02

     Titanium Oxide 0.3

     Crosscarboxymethylcellulose Sodium 3

     Magnesium Stearate 5

Using the above ingredients were carried out in the same manner as in Example 1 to complete the preparation of a granule mixture of a total of 292.57 g of the cold therapeutic agent portion.

Example 1-2 Preparation of Double-Definition Cold Therapy Granule Mixture

     Component Content (g / 1,000T)

     Acetaminophen 200

     dl-maleic chlorpheniramine 1.25

     Pseudohydrophedrine Hydrochloride 15

     Caffeine anhydrous 8.33

     Light anhydrous silicic acid 10

     Microcrystalline Cellulose 25

     Vinyl Pyrrolidone / Vinyl Acetate Copolymer (Plasdone S-630) 8

     Hydroxypropyl Cellulose (HPC-L) 7

     Pigment 0.2

     Titanium Oxide 0.03

     Crosscarboxymethylcellulose Sodium 3

     Magnesium Stearate 5

Using the above ingredients was carried out in the same manner as in Example 1 to complete the preparation of a granule mixture of a total of 282.81 g of the cold therapeutic agent part.

Example 1-3 Preparation of Granule Mixture of Double-Defined Cold Therapeutics

     Component Content (g / 1,000T)

     Acetaminophen 200

     dl-maleic chlorpheniramine 1.25

     Pseudohydrophedrine Hydrochloride 15

     Light anhydrous silicic acid 10

     Microcrystalline Cellulose 25

     Vinyl Pyrrolidone / Vinyl Acetate Copolymer (Plasdone S-630) 8

     Hydroxypropyl Cellulose (HPC-L) 7

     Pigment 0.2

     Titanium Oxide 0.03

     Crosscarboxymethylcellulose Sodium 3

     Magnesium Stearate 5

Using the above ingredients was carried out in the same manner as in Example 1 to complete the preparation of a granule mixture of a total of 274.48 g of the cold therapeutic agent portion.

Example 1-4 Preparation of Double-Definition Cold Therapy Granule Mixture

     Component Content (g / 1,000T)

     Acetaminophen 200

     Hydrochloric acid hydrochloride 8

     Pseudohydrophedrine Hydrochloride 15

     DL-Methylephedrine Hydrochloride 10

     Microcrystalline Cellulose 25

     Vinyl Pyrrolidone / Vinyl Acetate Copolymer (Plasdone S-630) 8

     Hydroxypropyl Cellulose (HPC-L) 7

     Pigment 0.2

     Titanium Oxide 0.03

     Crosscarboxymethylcellulose Sodium 3

     Magnesium Stearate 5

Using the above ingredients was carried out in the same manner as in Example 1 to complete the preparation of a granule mixture of a total of 281.23 g of the cold therapeutic agent portion.

Example 2 Preparation of Granular Mixtures of Double-Vitamin Vitamin Parts

     Component Content (g / 1,000T)

     Vitamin C (97%) 85.8

     100 Sugar

     Lactose 13

     Undecided sucrose 20

     Pigment 0.4

     Flavoring Agents 10

     Light anhydrous silicic acid 10

     Vinyl Pyrrolidone / Vinyl Acetate Copolymer (Plasdone S-630) 2

     Hydroxypropyl Cellulose (HPC-L) 7.5

     Magnesium Stearate 5

Homogeneously mixes vitamin C, sugar for sugar, lactose, vinyl pyrrolidone / vinyl acetate copolymer (Plasdone S-630), hydroxypropylcellulose (HPC-L), hard silicic anhydride, microcrystalline sucrose, pigments and flavoring agents. After mixing for a minute, magnesium stearate was added and mixed again to complete the preparation of a granule mixture of 253.7 g of the total vitamin portion.

Example 2-1. Preparation of Granular Mixture of Double-Vitamin Vitamin Part

     Component Content (g / 1,000T)

     Vitamin C (97%) 85.8

     Sugar for direct hits 130

     Lactose 12.87

     Undecided sucrose 20

     Pigment 0.4

     Flavoring Agents 10

     Light anhydrous silicic acid 10

     Hydroxypropyl Cellulose (HPC-L) 7

     Magnesium Stearate 5

Using the above components was carried out in the same manner as in Example 2 to complete the preparation of a granule mixture of a total of 271.07 g of the vitamin portion.

Example 2-2. Preparation of Granular Mixture of Double-Vitamin Vitamin Part

     Component Content (g / 1,000T)

     Vitamin C (97%) 85.8

     Ludipress (BASF) 120

     Lactose 12.8

     Undecided sucrose 20

     Pigment 0.4

     Flavoring Agents 10

     Hydroxypropyl Cellulose (HPC-L) 7

     Magnesium Stearate 5

Using the above ingredients were carried out in the same manner as in Example 2 to complete the preparation of a granule mixture of a total of 261.0 g of the vitamin portion.

Example 3. Double Tablet Preparation

A total of 554.6 g of cold medicine granules prepared in Examples 1 and 2 and 253.7 g of a granular mixture of vitamin parts were prepared using a double tablet press (PICCOLA DC, RIVA) according to the preparation method of tablet terms in the Korean Pharmaceutical Regulations. g was formulated into double tablets.

The average mass of one tablet was 554.6 ± 6.9 mg. Hardness was 13.1 ± 1.8kp and wear and tear was less than 0.04%.

Example 3-1. Double tablet manufacturing

292.57 g of the cold therapeutic granules prepared in Examples 1-1 and 2-1 and 271.07 g of the granular mixture of the vitamin portion were prepared in the tablet preparation method of the Korean Pharmaceutical Formulation by using a double tablet press (PICCOLA DC, RIVA). Thus a total of 563.64 g were formulated in double tablets.

The average mass of one tablet was 563.6 ± 10.1 mg. Hardness was 13.4 ± 1.3kp and wear and tear was less than 0.03%.

Example 3-2. Double tablet manufacturing

282.81 g of the cold therapeutic granules prepared in Example 1-2 and Example 2-1 and 271.07 g of the granular mixture of the vitamin portion were prepared in the tablet manufacturing method of the Korean Pharmaceutical Formulation by using a double tablet press (PICCOLA DC, RIVA). A total of 553.88 g was thus formulated in double tablets.

The average mass of one tablet was 563.9 ± 9.5 mg. Hardness was 12.9 ± 1.2kp and wear and tear was less than 0.04%.

Example 3-3. Double tablet manufacturing

281.23 g of the cold therapeutic granules prepared in Examples 1-4 and 2-1 and 271.07 g of the granule mixture of the vitamin portion were prepared in the tablet preparation method of the Korean Pharmaceutical Formulation using a double tablet press (PICCOLA DC, RIVA). Thus a total of 552.3 g were formulated in double tablets.

The average mass of one tablet was 552.3 ± 11.1 mg. Hardness was 13.3 ± 1.5kp and wear and tear was less than 0.04%.

Example 3-4. Double tablet manufacturing

274.48 g of the cold therapeutic granules prepared in Examples 1-3 and 2-2 and 261.0 g of the granule mixture of the vitamin portion were prepared in the tablet preparation method of the Korean Pharmaceutical Formulation by using a double tablet press (PICCOLA DC, RIVA). A total of 535.48 g were formulated in double tablets accordingly.

The average mass of one tablet was 535.5 ± 9.8 mg. Hardness was 14.1 ± 1.6kp and wear and tear was less than 0.03%.

Example 4 Preparation of Transparent Coated Double Tablets

     Coating content (mg / T)

     AMB clear (Colorcon) 18

     Distilled Water 72

554.6g of the multi-coated drug double tablet containing vitamins prepared in Example 3 was coated with Hi-coater (Model: SFC-30N, SeJong) to complete the transparent coating. The coating speed was 10.9 rpm, spray pressure was 2.5 bar, air blowing speed was 246.0 m ³ / hr, and spraying speed was 16.7 g / min. The average weight of one finished tablet was 572.6 mg, and the shape and color of the double tablet could be visually confirmed by applying a transparent coating to the double tablet.

Example 4-1. Manufacture of Transparent Coated Double Tablet

     Coating content (mg / T)

     Hydroxypropyl Methyl Cellulose (HPMC) 16

     PEG 6000 2

     Distilled Water 72

Using the above ingredients was carried out in the same manner as in Example 4 was subjected to a transparent coating on 563.64 g of the multi-cold medicine double tablet containing the vitamin prepared in Example 3-1. The average weight of one finished tablet was 583.6 mg, and the shape and color of the double tablet could be visually confirmed by applying a transparent coating layer to the double tablet.

Example 5 Preparation of Transparent Coated Double Tablets Containing Sweeteners and Flavors

     Coating content (mg / T)

     Opadry YS-1-7006 (Colorcon) 3

     Acesulfame Potassium 0.42

     Flavoring Agent 1.26

     Distilled water 4

     Ethanol 16

Synthetic cold medicine containing vitamins prepared in Example 4 Transparent coating double coated tablets using Hi-coater (Model: SFC-30N, SeJong) to give taste and flavor to the double tablets containing sweetener and flavoring agent Second transparent coating was completed. In the condition of coating the tablets transparently, the rotation speed of the coating pan was 13.0 rpm, the spraying pressure was 2.5 bar, the air blowing speed was 247.0 m ³ / hr, and the spraying speed was 25.0 g / min. The weight of one tablet to complete the coating was about 577mg, and the transparent coating layer was coated on the double tablets to visually confirm the shape and color of the double tablets.

Example 5-1. Preparation of Transparent Coated Double Tablet Containing Sweetener and Flavor

     Coating content (mg / T)

     Opadry YS-1-7006 (Colorcon) 3

     Sucralose 0.3

     Flavoring 1.7

     Distilled water 4

     Ethanol 16

Using the above ingredients in the same manner as in Example 5 to complete the second transparent coating containing a sweetener and a flavoring agent in 583.64 g of a multi-coated clear transparent double coated tablet containing vitamins prepared in Example 4-1. The finished tablet weighed about 588.6 mg, and the double coated tablet coated the double tablet to visually confirm the shape and color of the double tablet, and when it was placed in the mouth, it felt and lasted for at least 10 seconds. .

Comparative Example 1. Preparation of General Tablet

300.9 g of the cold therapeutic granules prepared in Examples 1 and 2 and 253.7 g of the granule mixture of the vitamin portion were produced in the same manner, and a total of 554.6 g of the single-shot tableting machine (Model: NR.1.0006.82, KORSCH) was used. General tablets were compressed.

The mass of one tablet was 554.6 mg, the hardness was 13 ± 1kp, and the friability was less than 0.08%.

Comparative Example 2. Preparation of Coated Tablet

The general tablets of Comparative Example 1 were coated in the same manner as in Examples 4 and 5, respectively.

Experimental Example 1. Disintegration time measurement test

The disintegration test was conducted to check whether the standard drugs of the general medicine described in the Pharmacists' Regulations of the formulation prepared in Example 5 meet the disintegration criteria of the standard preparation instructions for cold medicine.

Disintegration Tester: ERWEKA ZT302

Disintegration test solution: pH 1.2, pH 4.0, pH 6.8 and 900 mL of distilled water

Temperature of Disintegration Test Solution: 37.0 ± 0.5 ℃

Applicable standard: Within 30 minutes (Uncoated), Within 60 minutes (Film coated)

TABLE 1

PH 1.2 PH 4.0 PH 6.8 Distilled water Example 3 14 mins 18 mins 17 mins 17 mins Example 4 20 minutes 24 mins 23 mins 23 mins Example 5 21 mins 25 mins 24 mins 24 mins

As shown in the results of Table 1, Example 5 of the film-transparent coating prescription according to the present invention meets the criteria without a significant difference from uncoated Example 3 and exhibits a rapid disintegration time can be expected fast drug efficacy through rapid dissolution.

Test Example 2 Dose Preference Test

In order to compare and evaluate the taste and aroma that the preparation prepared in Example 5 is actually taken by humans, a total of 15 sensory test agents were recorded after direct administration using Example 3 as a control.

The tablets were placed on the tongue in the mouth and swallowed saliva once, then put an appropriate amount of water in the mouth and swallowed with water through the throat. The feeling of taste is recorded in the table.

TABLE 2

Example 3 Example 5 Taste and smell good - 10 people Taste and smell a little - 4 people is average 2 people 1 person Taste and smell a little bad 6 people - Have a bad taste and aroma 7 people - total 15 people 15 people

In particular, Example 3 was uncoated uncoated, and it was found that chlorphenylamine and ephedrine-based drugs lead to a very bitter taste and mixed with the sour and bitter taste of vitamins.

As shown in the results of Table 2, the transparent coating double-jungjung containing the taste and aroma according to the present invention not only masks bad taste and aroma, but also appears to have improved taste and aroma as the role of lemon and sweeteners. When you take the medicine, you can expect to increase your compliance by eliminating the prejudice that it is not good for taste or smell.

Test Example 3 Acceleration Stability Test

Accelerated stability tests were performed to evaluate the physicochemical stability of the formulations of the present invention. For Example 5, Example 3 was selected as a comparative control agent for the coating, and Comparative Example 2 was selected and performed as a comparative control agent for the double tablet. The accelerated stability test was carried out in a commercially available form in PTP packaging and aluminum pack packaging in an accelerated stability tester to exclude the discoloration effect of the vitamin.

Acceleration Stability Tester: Life Tester FLT-600D (Fine Scientific Instruments)

Acceleration safety test conditions: 40.0 ℃, 75% RH

Applicable standard: Within 30 minutes (Uncoated), Within 60 minutes (Film coated)

The content of the most unstable vitamin C (ascorbic acid) was recorded in Table 3, 20 tablets were used in one test, and the analysis conditions were referred to U.S.P.

20 tablets were crushed, 400 mg of ascorbic acid was added to 100 mL of water, 25 mL of 2N sulfuric acid solution was added and mixed homogeneously, and then 3 mL of starch solution for titration was added and titrated with 0.1 N iodine solution. 0.1 N iodine corresponds to 8.806 mg of ascorbic acid (C6H8O6).

In addition, the hardness of the tablet was measured by using a hardness tester (Vankel VK20) to evaluate the phenomenon of tablet retreat according to the hygroscopicity and physical properties of the cold medicine and vitamin C. Ten tablets were used for one evaluation and are reported in Table 4 with the average of ten.

[Table 3] unit:%

Ascorbic acid (vitamin C) 0 months 1 month 2 months 4 months 6 months Example 3 104.3 ± 0.7 100.8 ± 0.5 95.8 ± 1.9 90.1 ± 2.8 82.2 ± 3.3 Example 5 104.1 ± 0.2 102.2 ± 0.4 100.2 ± 1.2 97.5 ± 1.3 95.1 ± 1.8 Comparative Example 2 104.4 ± 0.3 92.4 ± 0.9 88.4 ± 2.7 80.1 ± 4.9 69.2 ± 7.1

TABLE 4

Hardness, kp 0 months 1 month 2 months 4 months 6 months Example 3 12.8 ± 0.7 11.4 ± 1.4 11.1 ± 1.8 10.6 ± 1.3 9.7 ± 2.1 Example 5 13.1 ± 1.1 12.9 ± 1.0 12.8 ± 0.8 12.6 ± 1.1 12.1 ± 1.5 Comparative Example 2 13.8 ± 1.0 8.4 ± 2.3 3.8 ± 3.3 2.0 ± 1.9 1.8 ± 0.4

When the stability test was carried out with the uncoated tablet of Example 3, the content of ascorbic acid (vitamin C) was slightly decreased, and the color of the uncoated tablet was partially due to the fact that moisture was slightly impregnated after 4 months. There was a slight change or a slight swelling of the tablets.

In Comparative Example 2, even though the coating was applied, the tablets did not become tablets in one phase but tablets in general. Because of poor stability, the tablets swelled out and became soft.

On the other hand, when the stability test was carried out by the transparent coating of Example 5, the color of the vitamin layer was changed slightly until six months passed, but there was no sign of physical tablets.

The present invention provides a physicochemical stability to the tablet by separating and tableting the vitamin C and the cold therapeutic agent, and further provides stability by coating such a double tablet with a coating material for moisture proof. In addition, it is coated with additional coating materials containing sweetening and flavoring agents to increase patient compliance, and these coatings are transparent to provide visual effects of double tablets. In addition, the double tablets thus prepared are smaller in size and easier to take than capsules. Accordingly, the present invention provides a double tablet containing vitamin C and a cold treatment agent having increased stability while satisfying the taste and smell, and is very useful pharmaceutically.

Claims (20)

A first layer containing vitamins; And A bilayer tablet comprising a second layer comprising a second layer containing a cold therapeutic agent adsorbed on a porous inorganic carrier selected from the group consisting of microcrystalline cellulose, hard silicic anhydride, bentonite, titanium oxide, talc and mixtures thereof. The two-layered tablet of claim 1, further comprising a transparent coating layer formed on the bare tablets. The agent for treating colds according to claim 1 or 2, wherein the cold treatment agent is acetaminophen, ibuprofen, dexibuprofen, ethenamide, phenacetin, dextrose hydrobromide, noscarpine hydrochloride, trimethoquinol hydrochloride, d-maleic acid. Chlorphenylamine, Carboxy citrate citrate, Tifepidine citrate, Cloferastine hydrochloride, Fendizoic acid cloferastine, Tibenic acid tifepidine, ephedrine hydrochloride, phenylephedrine hydrochloride, guapenesine, guayacolsulfonic acid potassium, dl -Methylephedrine hydrochloride, salt lysozyme, ceratiopeptidase, pseudoephedrine hydrochloride, phenylpropanolamine, dipexamide, phenylaminopropanol hydrochloride, oxymethazolin, xylmethazolin and mixtures thereof Two-story tablet characterized in that the. The method according to claim 1 or 2, wherein the vitamin is vitamin C, vitamin A, vitamin B1 (chiamine), vitamin B2 (riboflavin), vitamin B3 (niacin, niacinamide, nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6 ( Pyridoxine), vitamin B9 (folic acid), vitamin B12 (cyanocobalamin), vitamin D (calciferol), vitamin E (tocopherol), vitamin H (biotin) or vitamin K (phylloquinone, menaquinone, menadione) and these Two-layered tablet characterized in that it is selected from the group consisting of a mixture of. The method of claim 2, wherein the transparent coating layer is polyvinyl alcohol (PolyVinyl Alcohol (PVA), hydroxypropyl methyl cellulose (HPMC), phthalic acid hydroxypropyl methyl cellulose (HPMCP) and methacrylate dimethylaminoethyl methacrylate methacrylate) A bilayer tablet, characterized in that it is formed from at least one coating substrate selected from the group consisting of polymers (Eudragit E). delete delete The two-layered tablet according to claim 1 or 2, wherein the first layer and the second layer contain different pigments. The bilayer tablet according to claim 2, wherein the weight ratio of the uncoated tablet to the transparent coating layer is 1: 0.01 to 0.1. delete delete Adsorbing the pulverized cold therapeutic active ingredient to a porous inorganic carrier selected from the group consisting of microcrystalline cellulose, hard silicic anhydride, bentonite, titanium oxide, talc, and mixtures thereof; And A method of producing a bilayer tablet comprising the step of forming an uncoated tablet comprising a first layer containing a vitamin and a second layer containing a granule mixture of the main ingredient adsorbed on the inorganic carrier. The method of claim 12, further comprising: coating uncoated tablets with a first transparent coating layer; And Coating the first transparent coating layer with a second transparent coating layer containing a sweetener and a flavoring agent. The method of claim 2, wherein the transparent coating layer is a first transparent coating layer formed on the uncoated tablet; And Two-layered tablet, characterized in that consisting of a second transparent coating layer formed on the first transparent coating layer. 15. The bilayer tablet of claim 14 wherein the first transparent coating layer is formed from hydroxypropylmethylcellulose and the second transparent coating layer is formed from polyvinyl alcohol. 15. The bilayer tablet of claim 14 wherein the second transparent coating layer comprises a sweetener selected from the group consisting of acesulfame potassium, aspartame, stevioside, sucralose, saccharin and mixtures thereof. 15. The bilayer tablet of claim 14, wherein the second transparent coating layer comprises a flavoring agent. 18. The bilayer tablet of claim 17 wherein the flavoring agent is a volatile aromatic oil. 17. The bilayer tablet of claim 16 wherein the weight ratio of second transparent coating layer to sweetener is from 1: 0.001 to 0.025. 18. The bilayer tablet of claim 17 wherein the weight ratio of second transparent coating layer to flavoring agent is from 1: 0.02 to 0.8.